B cells: a fundamental role in the pathogenesis of rheumatoid arthritis?

The role of T cells in the pathogenesis of RA is well established, whereas to date the precise contribution of B cells is less well defined. B cells have many potential key roles: they can act as antigen-presenting cells, secrete pro-inflammatory cytokines (including tumour necrosis factor-alpha), produce rheumatoid factor (RF) and other autoantibodies and activate T cells. B cells act as antigen-presenting cells by processing and presenting antigenic peptides to T cells, which become activated, proliferate and exert pro-inflammatory activities. RF may also play a role in perpetuating B-cell activation and antigen presentation to T cells, thus leading to sustained production of RF. This, combined with RF immune-complex-mediated complement activation, may contribute to the sustained inflammatory response. Studies have shown that the use of an anti-CD20 monoclonal antibody in RA depletes circulating B cells, resulting in improvement in disease activity for up to 1 yr. It is thus evident that B cells play a central role in the pathophysiology of RA and therefore merit further investigation as a therapeutic target.